Despite the fact that androgen deprivation therapy (ADT) can effectively reduce prostate cancer (PCa) size, its effect on PCa metastasis remains unclear. We examined the existing data of PCa patients treated with ADT with anti-androgens to analyze therapy effects on primary tumors size, prostate specific antigen (PSA) values, and metastatic incidence. We found the current ADT with anti-androgens might lead to primary tumors reduction with PSA decreased yet metastases increased in some PCa patients. Using in vitro and in vivo metastasis models with human 4 PCa cell lines, we evaluated the effects of the currently used anti-andrgoens, Casodex and MDV3100, and the newly developed anti-AR compounds, ASC-J9 and cryptotanshinone (CTS), on PCa cell growth and invasion. In vitro results showing that 10 μM Casodex or MDV3100 treatments suppressed PCa cell growth and reduce PSA level, yet significantly enhanced PCa cells invasion. In vivo mice studies using orthotopic xenograft mouse model also confirmed these results. In contrast, ASC-J9 led to suppress PCa cell growth and cell invasion in in vitro and in vivo models. Mechanism dissection indicated these Casodex/MDV3100 treatments enhanced the TGF-β1/Smad3/MMP9 pathway, but ASC-J9 and CTS showed promising anti-invasion effects via downregulation of MMP9 expression. These findings suggest the potential risks of using anti-androgens and provide a potential new therapy using ASC-J9 to battle PCa metastasis at the castration resistant stage.